Physical activity is a common stressor experienced during pregnancy. For ethical and technical reasons, it is difficult to directly investigate the uterine blood flow response to exercise in pregnant women. The overall goal of this proposal is to investigate putative mechanisms underlying the observation that term pregnancy in the rabbit is associated with an attenuated uterine vasoconstrictor response to dynamic treadmill exercise. Aim 1. To test the hypothesis that attenuation of the uterine artery vasoconstrictor response to exercise is evident at early and mid-gestation. Aim 2. To test the hypothesis that the gestational attenuation of the uterine artery vasoconstrictor response to exercise is dependent on the presence of a developing fetoplacental unit in the ipsilateral uterine horn. Aim 3. To test the hypothesis that alpha-adrenoceptor and NPY Y1 receptor mediated processes contribute to the uterine artery vasoconstrictor response to exercise throughout gestation. Aim 4. To test the hypothesis that endogenous NO production opposes uterine artery vasconstriction during exercise and that the influence of this dilator system on the vasoconstrictor response to exercise is magnified during normal pregnancy. NZW female rabbits are studied longitudinally in the NP state and during pregnancy at early, mid and term gestation (Aim 1). Rabbits are surgically instrumented with flowprobes on the right and left uterine arteries to measure blood flow to the uterine horns, and one oviduct is ligated, to prevent pregnancy in that horn. Thus, upon breeding, rabbits will carry fetuses in only one uterine horn. This will allow a separation of the influence of the physical presence of a developing fetus from systemic factors on the adaptation of the uterine circulation to exercise in pregnancy (Aim 2). Rabbits are exercised on a motorized treadmill. Rabbits are divided into 4 groups and are assigned to one of four exercise protocols. The protocols are: alpha-adrenergic antagonism (Aim 3), NPY Y1 receptor antagonism (Aim 3), nitric oxide synthase inhibition (Aim 4) and an exercise time control (no drug treatment). Successful completion of these aims will advance our understanding of uterine circulatory control during exercise in normal pregnancy, and may provide insight into the mechanisms underlying abnormal circulatory responses to physical activity in pregnancies complicated by preeclampsia and other hypertensive conditions.